Potassium Carbonate → tert-Butyl 4-[(2-{4-[5-chloro-2-(trifluoromethyl)phenyl]-5-methoxy-2-oxopyridin-1(2H)-yl}propanoyl)amino]benzoate

HRID 56840Notes

Reaction equation

HRID 56840 reaction equation
Br[C:2]1[C:7]([O:8][CH3:9])=[CH:6][N:5]([CH:10]([CH3:27])[C:11]([NH:13][C:14]2[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:16][CH:15]=2)=[O:12])[C:4](=[O:28])[CH:3]=1.[Cl:29][C:30]1[CH:31]=[CH:32][C:33]([C:39]([F:42])([F:41])[F:40])=[C:34](B(O)O)[CH:35]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1>[Cl:29][C:30]1[CH:31]=[CH:32][C:33]([C:39]([F:40])([F:41])[F:42])=[C:34]([C:2]2[C:7]([O:8][CH3:9])=[CH:6][N:5]([CH:10]([CH3:27])[C:11]([NH:13][C:14]3[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:16][CH:15]=3)=[O:12])[C:4](=[O:28])[CH:3]=2)[CH:35]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 467368175-Chloro-2-(trifluoromethyl)phenylboronic acid2×HCID 117622877tert-Butyl 4-{[2-(4-bromo-5-methoxy-2-oxopyridin-1(2H)-yl)propanoyl]amino}benzoate

Product 1

HCID 117622759tert-Butyl 4-[(2-{4-[5-chloro-2-(trifluoromethyl)phenyl]-5-methoxy-2-oxopyridin-1(2H)-yl}propanoyl)amino]benzoate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Under argon (in a flask dried by heating), 113 mg (0.25 mmol) of tert-butyl 4-{[2-(4-bromo-5-methoxy-2-oxopyridin-1(2H)-yl)propanoyl]amino}benzoate (racemate), 67 mg (0.30 mmol, 1.2 eq.) of 5-chloro-2-trifluoromethylphenylboronic acid, 103 mg (0.74 mmol, 3.0 eq.) of potassium carbonate and 20 mg (0.03 mmol, 0.1 eq.) of [1,1-bis(diphenylphosphino)ferrocene]palladium(II) chloride/dichloromethane monoadduct were suspended in 5.0 ml of dioxane and stirred overnight in an oil bath already preheated to 110° C. A further 10 mg (0.01 mmol, 0.05 eq.) of [1,1-bis-(diphenylphosphino)ferrocene]palladium(II) chloride/dichloromethane monoadduct and 22 mg (0.10 mmol, 0.4 eq.) of 5-chloro-2-trifluoromethylphenylboronic acid were added and the reaction mixture was stirred at 110° C. for a further 20 h and then filtered through Celite. The residue was washed with dioxane. The combined filtrates were concentrated under reduced pressure. The residue was triturated with water, filtered off, washed with water and dried under reduced pressure. Yield: 145 mg (purity 84%, 89% of theory)

Workup

  1. customalready preheated to 110° C
  2. stirringthe reaction mixture was stirred at 110° C. for a further 20 h
  3. filtrationfiltered through Celite
  4. washThe residue was washed with dioxane
  5. concentrationThe combined filtrates were concentrated under reduced pressure
  6. customThe residue was triturated with water
  7. filtrationfiltered off
  8. washwashed with water
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-288b68c914574ba6a8f045ac1752c5da
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Reaction notes

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